Genetic analysis of products of conception using a HLPA/SNP-array strategy

Mao, Jun; Wang, Huiling; Li, Haibo; Song, Xiaoyan; Wang, Ting; Xiang, Jingjing; Li, Hong

doi:10.1186/s13039-019-0452-2

Cited by 8 publications

(10 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A total of 564 CNVs less than 3 Mb (mean: 690.2 Kb, ranging from 6.4 Kb to 2.98 Mb) were obtained from 442 euploid POCs, of which 176 CNVs were detected in our institution and 266 were extracted from 19 peer-reviewed publications ( Supplementary Figure S1 ). All CNVs were detected using SNP array (9 research studies) ( Reddy et al, 2012 ; Kooper et al, 2014 ; Wang et al, 2017 ; Qi et al, 2018 ; Zhu et al, 2018 ; Mao et al, 2019 ; Sato et al, 2019 ; Yang et al, 2019 ; Wang et al, 2020 ), array CGH (4 research studies) ( Shimokawa et al, 2006 ; Deshpande et al, 2010 ; Rajcan-Separovic et al, 2010 ; Donaghue et al, 2017 ), or CMA (6 research studies plus our data) ( Sahlin et al, 2014 ; Wang et al, 2014 ; Rosenfeld et al, 2015 ; Parchem et al, 2018 ; Chau et al, 2020 ; Zhang et al, 2021 ). The threshold of those studies called the CNVs has been reported ranging from 50 to 135 Kb.…”

Section: Resultsmentioning

confidence: 99%

Copy Number Variation Analysis of Euploid Pregnancy Loss

Gao

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Objectives: Copy number variant (CNV) is believed to be the potential genetic cause of pregnancy loss. However, CNVs less than 3 Mb in euploid products of conceptions (POCs) remain largely unexplored. The aim of this study was to investigate the features of CNVs less than 3 Mb in POCs and their potential clinical significance in pregnancy loss/fetal death.Methods: CNV data were extracted from a cohort in our institution and 19 peer-reviewed publications, and only those CNVs less than 3 Mb detected in euploid pregnancy loss/fetal death were included. We conducted a CNV map to analyze the distribution of CNVs in chromosomes using R packages karyoploteR_1.10.5. Gene names and annotated gene types covered by those CNVs were mined from the human Release 19 reference genome file and GENECODE database. We assessed the expression patterns and the consequences of murine knock-out of those genes using TiGER and Mouse Genome Informatics (MGI) databases. Functional enrichment and pathway analysis for genes in CNVs were performed using clusterProfiler V3.12.0.Result: Breakpoints of 564 CNVs less than 3 Mb were obtained from 442 euploid POCs, with 349 gains and 185 losses. The CNV map showed that CNVs were distributed in all chromosomes, with the highest frequency detected in chromosome 22 and the lowest frequency in chromosome Y, and CNVs showed a higher density in the pericentromeric and sub-telomeric regions. A total of 5,414 genes mined from the CNV regions (CNVRs), Gene Ontology (GO), and pathway analysis showed that the genes were significantly enriched in multiple terms, especially in sensory perception, membrane region, and tight junction. A total of 995 protein-coding genes have been reported to present mammalian phenotypes in MGI, and 276 of them lead to embryonic lethality or abnormal embryo/placenta in knock-out mouse models. CNV located at 19p13.3 was the most common CNV of all POCs.Conclusion: CNVs less than 3 Mb in euploid POCs distribute unevenly in all chromosomes, and a higher density was seen in the pericentromeric and sub-telomeric regions. The genes in those CNVRs are significantly enriched in biological processes and pathways that are important to embryonic/fetal development. CNV in 19p13.3 and the variations of ARID3A and FSTL3 might contribute to pregnancy loss.

show abstract

Section: Resultsmentioning

confidence: 99%

Copy Number Variation Analysis of Euploid Pregnancy Loss

Gao

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…The Affymetrix CytoScan platform (Affymetrix, Santa Clara, CA, USA) was used for SNP array analysis using a previously described method [ 19 ]. Genomic DNA (250 ng) was digested, ligated, PCR-amplified, purified, fragmented, labeled, and hybridized to the Affymetrix 750 K array, which included 550,000 CNV markers and 200,000 SNP markers.…”

Section: Methodsmentioning

confidence: 99%

A fetal fraction enrichment method reduces false negatives and increases test success rate of fetal chromosome aneuploidy detection in early pregnancy loss

Qiao

Zhang

et al. 2022

J Transl Med

Self Cite

View full text Add to dashboard Cite

Objective We and others have previously demonstrated that the size-selection enrichment method could remarkably improve fetal fraction (FF) in the early gestational age (GA, 12–13 weeks), suggesting that 9 or 10 weeks should not be used as a threshold for GA in size-selection noninvasive prenatal screening (NIPS). Here, we assessed whether this method was reliable for detecting fetal chromosomal aneuploidy at the earliest GA (6–8 weeks). Methods Size-selection NIPS for fetal chromosomal aneuploidy was applied to 208 pregnancy plasma samples (102 male and 106 female fetuses), while the 169 pregnancy samples with male fetuses also underwent standard NIPS. Multivariable linear regression models were used to evaluate the association between fold-change of FF and experimental factors. Results The sensitivity of the cell-free DNA (cfDNA) test in detecting aneuploidy was 100% when screened with FF enrichment, whereas the sensitivity of the same patients was only 62.5% (5/8) without FF enrichment. In the 102 pregnancy samples with male fetuses, FF increased from 6.1% to 15.7%, and the median increase in FF was 2.8-fold with enrichment. Moreover, there was a trend toward an increasing success rate of the cfDNA test from 6 to 13 weeks of gestation, especially when the test success rate reached 100% after 7 weeks with FF enrichment. Multivariate linear regression analysis demonstrated that a lower initial FF, shorter cfDNA size, increased body mass index (BMI), and later GA were all independent predictors of a higher fold-change of FF. Compared with ≤ 120 bp cfDNA fragments, the mean fold-change of FF differences was 0.820 for 121–125 bp, 0.229 for 126–130 bp, − 0.154 for 131–135 bp, − 0.525 for 136–140 bp and − 0.934 for > 140 bp (Ptrend < 0.0001), suggesting that fold-change of FF significantly decreased with cfDNA fragments > 125 bp. These results were statistically significant after adjusting for confounding factors in the models for fold-change of FF. Conclusions The FF enrichment method is a reasonable strategy to detect fetal chromosomal aneuploidy in early pregnancy loss with reduced false negatives and increased test success rate after 7 weeks of GA and should be recommended for patients with early pregnancy loss.

show abstract

“…Molecular karyotyping was performed by CytoScan HD Arrays (Affymetrix, Santa Clara, CA, USA) consisting of about 2.7 million markers. All the procedures have been repeatedly described in detail previously [21,22,56,57]. Cytogenomic variations were visualized using the Affymetrix ChAS (Chromosome Analysis Suite) software (CytoScan ® HD Array Version 4.1.0.90/r29400).…”

Section: Snp-arraymentioning

confidence: 99%

The Cytogenomic “Theory of Everything”: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and Aging

Iourov

Vorsanova

Yurov

et al. 2020

IJMS

View full text Add to dashboard Cite

Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are not completely understood. During molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n = 612), we observed colocalization of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n = 47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as “chromohelkosis” (from the Greek words chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either in partial/whole chromosome loss (e.g., aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g., prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything”, similar to the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.

show abstract

Genetic analysis of products of conception using a HLPA/SNP-array strategy

Cited by 8 publications

References 19 publications

Copy Number Variation Analysis of Euploid Pregnancy Loss

Copy Number Variation Analysis of Euploid Pregnancy Loss

A fetal fraction enrichment method reduces false negatives and increases test success rate of fetal chromosome aneuploidy detection in early pregnancy loss

The Cytogenomic “Theory of Everything”: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and Aging

Contact Info

Product

Resources

About